Protective role of D-saccharic acid-1,4-lactone in alloxan induced oxidative stress in the spleen tissue of diabetic rats is mediated by suppressing mitochondria dependent apoptotic pathway

Abstract

The present study investigated the role of D-saccharic acid 1,4-lactone (DSL) in the spleen tissue of alloxan (ALX) induced diabetic rats. Diabetes was induced in rats by injecting ALX (at a dose of 120 mg/kg body weight) intraperitoneally in sterile normal saline. Elevated levels of blood glucose, glycosylated Hb and TNFα decreased levels of plasma insulin and disturbed intra-cellular antioxidant machineries were detected in ALX exposed animals. Oral administration of DSL at a dose of 80 mg/kg body weight, however, restored these alterations in diabetic rats. Studies on the mechanism of ALX-induced diabetes showed that hyperglycemia caused disruption of mitochondrial membrane potential in the spleen, released cytochrome C in the cytosol, activated caspase 3 and ultimately led to apoptotic cell death. Results suggest that DSL possesses the ability of protecting the spleen tissue from ALX-induced hyperglycemia and thus could act as an anti-diabetic agent in lessening diabetes associated spleen dysfunction.

Keywords::

• Alloxan
• hyperglycemia
• oxidative stress
• spleen
• mitochondrial dependent apoptosis
• D-saccharic acid 1, 4-lactone
• antiapoptotic

This paper was first published online on Early Online on 18 January 2012.